Airway epithelial cell inflammatory signalling in cystic fibrosis

摘要: Cystic fibrosis (CF) is the most common lethal monogenic disorder in Caucasians, estimated to affect one out of 2500-4000 new-borns. In patients with CF, lack CF transmembrane conductance regulator (CFTR) Cl(-) channel function leads progressive pulmonary damage and ultimately death. Severe persistent polymorphonuclear neutrophil-dominated endobronchial inflammation chronic bacterial infection are characteristic hallmarks lung disease. Whether CFTR dysfunction results directly an increased predisposition whether arises independent remains be established. The loss functional airway epithelial cells promotes depletion oxidation surface liquid. Activated neutrophils present airways produce large amounts proteases reactive oxygen species (ROS). Together these changes associated diminished mucociliary clearance bacteria, activation cell signalling through multiple pathways, subsequent hyperinflammatory responses airways. NF-kappaB pathway Ca(2+) mobilization believed key importance for control regulated production mediators such as interleukin-8 that participate recruitment neutrophils, modulation apoptosis, barrier integrity. this review, current understanding molecular mechanisms by which contribute abnormal well anti-inflammatory strategies can proposed discussed.